Recently, researchers and clinicians have focused increased attention on a group of children with severe mood and behavioral dysregulation (SMD). These children are characterized by impairing symptoms that include abnormal baseline mood (i.e. irritability, anger, and/or sadness), hyperarousal (e.g. insomnia, agitation, distractibility), and increased reactivity to negative emotional stimuli. Because this syndrome shares many clinical features with bipolar disorder (BPD), there is considerable debate as to whether these children should be diagnosed with BPD. However, children with this syndrome lack the cardinal symptoms of BPD, and other DSM-IV diagnoses (ADHD, ODD, etc.) capture heterogeneous clinical populations that include many children who do not exhibit the symptoms noted above. Therefore, the goals of this project are 1) to identify reliably a group of children with severe mood and behavioral dysregulation in order to characterize them clinically and behaviorally, and follow them longitudinally, 2) to compare the brain function of SMD children (assessed with functional MRI and standardized behvioral testing)to that of children with unequivocal BPD; 3) to conduct a double-blinded, placebo-controlled trial of lithium in children with SMD. Standardized interview modules and rating scales will be used to rate the clinical features of mood dysregulation. A double-blind, placebo-controlled trial of lithium will be conducted, and magnetic resonance spectroscopy (MRS) will be preformed before and after treatment to ascertain effects of lithium treatment on brain metabolites. Approximately 15 patients have completed the treatment trial, and MRS scans have been obtained. Data from standardized behavioral paradigms have been obtained on approximately 80 children with SMD in order to identify deficits in core psychological processes associated with the disorder. In addition, functional MRI data have been obtained on approximately 40 SMD children on paradigms that have also been used in children with BPD and ADHD. The fMRI data are currently being analyzed. The behavioral adata show that children with SMD have face emotion labeling deficits that are similar to those of children with BPD. However, children with SMD, but not those with BPD, have deficits in their responses to punishing stimuli. Data also indicate that children with SMD differ from those with BPD in their psychophysiological and behavioral responses to frustration, although the affective responses of the two patient groups are similar. A post-hoc analysis of data from two longitudinal epidemiological studies indicate that children with SMD are more likely than non-SMD children to meet criteria for depression, but not BPD, in early adulthood.